Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (A)

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Co-administration of Saxagliptin and Metformin IR, Fed; Drug: Saxagliptin/Metformin, Fed; Drug: Saxagliptin/Metformin, Fasting; Drug: Co-administration of Saxagliptin and Metformin IR, Fasted

Study type: Interventional

Funder types: Industry

Identifiers

NCT00899470

CV181-081

Details and patient eligibility

About

To demonstrate bioequivalence of a 2.5 mg saxagliptin/500 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 500 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.

Enrollment: 24 patients

Sex: All

Ages: 19 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Men and women ages 19 to 45 inclusive
• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2

Exclusion criteria

• Women of child-bearing potential (WOCBP) who are unwilling or unable to use acceptable barrier methods (condoms and spermicides) to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product
• Any significant acute or chronic medical illness
• Current or recent (within 3 months) gastrointestinal disease
• Any major surgery within 4 weeks of study drug administration
• History of allergy to Dipeptidyl peptidase 4 (DPP4) inhibitor or related compounds
• History of allergy or intolerance to metformin or other similar acting agents
• Prior exposure to saxagliptin
• Prior exposure to metformin within 3 months of study drug administration.
• Estimated creatinine clearance (Clcr) of < 80ml/min using the Cockcroft Gault formula

Trial design

24 participants in 4 patient groups

S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)

Experimental group

Description:

Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\])

Treatment:

Drug: Saxagliptin/Metformin, Fed

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted

Drug: Co-administration of Saxagliptin and Metformin IR, Fed

Drug: Saxagliptin/Metformin, Fasting

S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)

Experimental group

Description:

Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)

Treatment:

Drug: Saxagliptin/Metformin, Fed

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted

Drug: Co-administration of Saxagliptin and Metformin IR, Fed

Drug: Saxagliptin/Metformin, Fasting

S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)

Experimental group

Description:

Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)

Treatment:

Drug: Saxagliptin/Metformin, Fed

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted

Drug: Co-administration of Saxagliptin and Metformin IR, Fed

Drug: Saxagliptin/Metformin, Fasting

S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)

Experimental group

Description:

Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)

Treatment:

Drug: Saxagliptin/Metformin, Fed

Drug: Co-administration of Saxagliptin and Metformin IR, Fasted

Drug: Co-administration of Saxagliptin and Metformin IR, Fed

Drug: Saxagliptin/Metformin, Fasting